Air pollution particles have a deleterious effect on respiratory health and have been linked to exacerbated pulmonary inflammation and infection. As most of these particles do not stimulate humoral responses, they are cleared by alveolar macrophage scavenger receptors. While this process is important for maintaining respiratory health, it is not well understood. This proposal delineates experiments designed to (i) characterize the ultrastructural morphology, molecular components and signaling pathways associated with scavenger receptor mediated phagocytosis and (ii) determine the roles of accessory molecules and receptor cooperation in this process. The first goal will be achieved using electron and confocal microscopic analysis of the phagocytic synapse as well as pharmacological signaling pathway inhibitors. The second goal will be accomplished using CHO-K1 cells co-transfected with SR-AI or MARCO along with the Fc gamma chain or the type 3 complement receptor (both of which are promiscuous phagocytic signaling molecules). Receptor cooperativity will be investigated using transfected fluorescent receptor fusion proteins. Finally, a novel proteomic technique will be used to identify new proteins present in the phagocytic synapse. [unreadable] [unreadable]